3052 - Radiotherapy-Induced Myeloid Infiltration in the Visual Pathway: A Histopathologic Analysis
Presenter(s)
A. Grosinger1, D. Bedell2, L. Golden1, N. Sando1, J. Lawrence3, S. R. Alcorn1, J. Moore1, A. Venteicher4, S. A. Terezakis1, L. Chen2, and L. Sloan1; 1University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, 2University of Minnesota: Department of Laboratory Medicine and Pathology, Minneapolis, MN, 3Masonic Cancer Center, Minneapolis, MN, 4University of Minnesota: Department of Neurosurgery, Minneapolis, MN
Purpose/Objective(s): Radiation-induced optic neuropathy (RION) is a rare and irreversible consequence of radiotherapy (RT) affecting the visual pathway, with the risk increasing when conventionally fractionated RT (CF RT) doses exceed 50 Gy. Although the precise cause remains uncertain, one proposed explanation involves immune cell infiltration into visual structures. Myeloid cell infiltration into brain tissue is a known effect of CF RT, yet its specific impact on optic structures vulnerable to RION is not well understood. This study aims to assess the frequency of myeloid cells in tumor tissue within the visual pathway that has received 50 Gy CF RT, comparing it to non-tumor controls with no history of RT. We hypothesize that myeloid infiltration in irradiated tumor tissue will be greater than that observed in non-irradiated, non-tumor tissue.
Materials/Methods: We acquired formalin-fixed, paraffin-embedded tissue samples from patients aged 18 or older who had been diagnosed with either malignant or benign tumors affecting visual pathway structures, including the eye, optic nerves, chiasm, and optic radiations. These patients had previously undergone CF RT at doses of 50 Gy or higher. These were compared to age, sex, and location matched pathology controls of patients without tumors. Immunohistochemistry (IHC) was conducted using CD68-targeted antibodies. The number of positively stained cells within tumor tissue and non-tumor control samples was quantified per high-power field (HPF). A two-tailed t-test was used to compare the mean number of positive cells.
Results: Seven patients underwent CF RT, with prescribed doses varying between 50 and 85 Gy. The median patient age was 58 years (range 52–68), with three being male. The median interval from RT completion to resection was 451.5 days (range 50–1,272). Among the seven patients who underwent CF RT, six were new or recurrent glioblastomas and one was a choroidal melanoma. Seven control patients did not receive CF RT. The median control patient age was 56 (range 55-69) with four being male. The mean myeloid cells per HPF staining positively for tumor tissue that invaded optic structures and control tissues was different for CD68 (50.9 vs. 12.0, p<0.001).
Conclusion: Initial findings indicate a statistically significant variation in myeloid cell staining found in tumor tissue of the visual pathway that received at least 50 Gy of CF RT and matched non-radiated control tissue. A limitation of this study is that neuroinflammation is known to occur in non-tumor pathologies that may have been present in control tissues. For our next steps, we will expand upon this data by investigating further IHC studies of myeloid phenotypes as well as clinical toxicity with myeloid infiltrates. A deeper investigation into myeloid cell infiltration within the visual pathway could enhance our understanding of the mechanisms underlying RION, potentially uncovering key neuroprotective agents for future clinical applications.